期刊文献+

EGFR gene copy number as a predictive biomarker for resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer treatment:a meta-analysis 被引量:2

EGFR gene copy number as a predictive biomarker for resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer treatment:a meta-analysis
下载PDF
导出
摘要 Objective:The epidermal growth factor receptor (EGFR) inhibitors monoclonal antibodies (MoAbs) have already shown the therapeutic effectiveness in patients with metastatic colorectal cancer (mCRC).But many patients resist to the treatment.The aim of this meta-analysis was to assess EGFR gene copy number (GCN) as a candidate predictive biomarker for resistance to anti-EGFR MoAbs in mCRC treatment.Methods:Systematic computerized searches of the PubMed,EMBase and Cochrane Library were performed.The primary endpoint was objective response rate (ORR).The second endpoints included progression-free survival (PFS),and overall survival (OS).The pooled odd ratio (OR) and pooled sensitivity,specificity,and summary receiver operator characteristic (SROC) for ORR were estimated.The pooled hazard ratios (HR) for PFS and OS were also calculated.Results:Fourteen studies with 1,021 patients were included.Increased EGFR GCN was associated with increased ORR (OR=6.905; 95% CI:4.489-10.620).It was also found in wild-type KRAS mCRC patients,with the pooled OR of 8.133 (95 % CI:4.316-15.326).GCN has medium value for predicting ORR,with the pooled sensitivity of 0.79 (95% CI:0.73-0.84),the pooled specificity of 0.59 (95% CI:0.55-0.62).In wildtype KRAS mCRC patients,the sensitivity and the specificity were 0.80 (95% CI:0.70-0.87) and 0.60 (95%CI:0.53-0.66),respectively.Increased EGFR GCN was associated with increased PFS (HR=0.557; 95% CI:0.382-0.732) and OS (HR=0.579; 95% CI:0.422-0.737).Conclusions:This meta-analysis suggests that EGFR GCN represents a predictive biomarker for tumor response in mCRC patients treated with MoAbs regardless of KRAS mutation.mCRC patients with increased EGFR GCN are more likely to have a better response,PFS,and OS when treated with cetuximab or panitumumab. Objective:The epidermal growth factor receptor (EGFR) inhibitors monoclonal antibodies (MoAbs) have already shown the therapeutic effectiveness in patients with metastatic colorectal cancer (mCRC).But many patients resist to the treatment.The aim of this meta-analysis was to assess EGFR gene copy number (GCN) as a candidate predictive biomarker for resistance to anti-EGFR MoAbs in mCRC treatment.Methods:Systematic computerized searches of the PubMed,EMBase and Cochrane Library were performed.The primary endpoint was objective response rate (ORR).The second endpoints included progression-free survival (PFS),and overall survival (OS).The pooled odd ratio (OR) and pooled sensitivity,specificity,and summary receiver operator characteristic (SROC) for ORR were estimated.The pooled hazard ratios (HR) for PFS and OS were also calculated.Results:Fourteen studies with 1,021 patients were included.Increased EGFR GCN was associated with increased ORR (OR=6.905; 95% CI:4.489-10.620).It was also found in wild-type KRAS mCRC patients,with the pooled OR of 8.133 (95 % CI:4.316-15.326).GCN has medium value for predicting ORR,with the pooled sensitivity of 0.79 (95% CI:0.73-0.84),the pooled specificity of 0.59 (95% CI:0.55-0.62).In wildtype KRAS mCRC patients,the sensitivity and the specificity were 0.80 (95% CI:0.70-0.87) and 0.60 (95%CI:0.53-0.66),respectively.Increased EGFR GCN was associated with increased PFS (HR=0.557; 95% CI:0.382-0.732) and OS (HR=0.579; 95% CI:0.422-0.737).Conclusions:This meta-analysis suggests that EGFR GCN represents a predictive biomarker for tumor response in mCRC patients treated with MoAbs regardless of KRAS mutation.mCRC patients with increased EGFR GCN are more likely to have a better response,PFS,and OS when treated with cetuximab or panitumumab.
出处 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2014年第1期59-71,共13页 中国癌症研究(英文版)
关键词 Metastatic colorectal cancer (mCRC) epidermal growth factor receptor (EGFR) gene copy number (GCN) META-ANALYSIS Metastatic colorectal cancer (mCRC) epidermal growth factor receptor (EGFR) gene copy number (GCN) meta-analysis
  • 相关文献

参考文献44

  • 1Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012,62:10-29.
  • 2Jemal A, Bray F, Center MM, et al. Global cancer statistics.CA Cancer J Clin 2011,669_90.".
  • 3Grothey A, Marshall JL. Optimizing palliative treatment of metastatic colorectal cancer in the era of biologic therapy. Oncology (Williston Park) 2007,21:553-64.
  • 4Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. Clin Onco12005,23:2445-59.
  • 5Cunningham D, Humblet Y, Siena S, et al. Ceximab monotherapy and cetuximab plus irinotecan in irinotecan- refractory metastatic colorectal cancer. N Engl J Med 2004,351:337-45.
  • 6Van Cutsem E, K6hne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N EnglJ Med 2009,360:1408-17.
  • 7Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Onco12007,25:1658-64.
  • 8Johnson KR, Ringland C, Stokes BJ, et al. Response rate or time to progression as predictors of survival in trials of metastatic colorectal cancer or non-small-cell lung cancer a meta-analysis. Lancet Onco12006,7:741-6.
  • 9Linardou H, Dahabreh rJ, Kanaloupiti D, et al. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small- cell lung cancer and metastatic colorectal cancer. Lancet Oncol 2008,9:962-72.
  • 10Siena S, Sartore-Bianchi A, Di Nicolantonio F, et al. Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 2009, 101:1308-24.

同被引文献9

引证文献2

二级引证文献8

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部